tbuckley/cabot-search huggingface dataset:
A large language model for electronic health records
Authors: Xi Yang, Aokun Chen, Nima PourNejatian, Hoo Chang Shin, Kaleb E. Smith, Christopher Parisien, Colin Compas, Cheryl Martin, Anthony B. Costa, Mona G. Flores, Ying Zhang, Tanja Magoc, Christopher A. Harle, Gloria Lipori, Duane A. Mitchell, William R. Hogan, Elizabeth A. Shenkman, Jiang Bian, Yonghui Wu
Journal: npj Digital Medicine (2022)

Abstract There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model—GatorTron—using &gt;90 billion words of text (including &gt;82 billion words of de-identified clinical text) and systematically evaluate it on five clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve five clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og .
Author Correction: Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice
Authors: Lingfeng Shi, Yixiang Li, Xiaoli Xu, Yangyang Cheng, Biying Meng, Jinling Xu, Lin Xiang, Jiajia Zhang, Kaiyue He, Jiayue Tong, Junxia Zhang, Lingwei Xiang, Guangda Xiang
Journal: Nature Metabolism (2022)
Leukemia inhibitory factor, a double-edged sword with therapeutic implications in human diseases
Authors: Jianming Wang, Chun-Yuan Chang, Xue Yang, Fan Zhou, Juan Liu, Zhaohui Feng, Wenwei Hu
Journal: Molecular Therapy (2022)

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 (IL-6) superfamily. LIF was initially discovered as a factor to induce the differentiation of myeloid leukemia cells and thus inhibit their proliferation. Subsequent studies have highlighted the multi-functions of LIF under a wide variety of physiological and pathological conditions in a highly cell-, tissue-, and context-dependent manner. Emerging evidence has demonstrated that LIF plays an essential role in the stem cell niche, where it maintains the homeostasis and regeneration of multiple somatic tissues, including intestine, neuron, and muscle. Further, LIF exerts a crucial regulatory role in immunity and functions as a protective factor against many immunopathological diseases, such as infection, inflammatory bowel disease (IBD), and graft-verse-host disease (GVHD). It is worth noting that while LIF displays a tumor-suppressive function in leukemia, recent studies have highlighted the oncogenic role of LIF in many types of solid tumors, further demonstrating the complexities and context-dependent effects of LIF. In this review, we summarize the recent insights into the roles and mechanisms of LIF in stem cell homeostasis and regeneration, immunity, and cancer, and discuss the potential therapeutic options for human diseases by modulating LIF levels and functions.
Pathological characteristics of light chain crystalline podocytopathy
Authors: Samih H. Nasr, Satoru Kudose, Vincent Javaugue, Stéphanie Harel, Samar M. Said, Virginie Pascal, M. Barry Stokes, Julie A. Vrana, Surendra Dasari, Jason D. Theis, George A. Osuchukwu, Insara Jaffer Sathick, Arjun Das, Ali Kashkouli, Elliot J. Suchin, Yaakov Liss, Zalman Suldan, Jerome Verine, Bertrand Arnulf, Alexis Talbot, Sanjeev Sethi, Mohamad Zaidan, Jean-Michel Goujon, Anthony M. Valeri, Ellen D. Mcphail, Christophe Sirac, Nelson Leung, Frank Bridoux, Vivette D. D’Agati
Journal: Kidney International (2022)
Socioeconomic inequalities in the risk of suicide attempts among sexual minority adolescents: findings from the UK's Millennium Cohort Study
Authors: James White, Sophie Borgia, David H. Rehkopf
Journal: The Lancet Regional Health - Europe (2022)

Both sexual minority and socioeconomically deprived young people are at an increased risk of making a suicide attempt. Intersectionality theory predicts these risk factors will interact synergistically to create unique vulnerabilities. We investigated the risk of suicide attempts in sexual minority socioeconomically deprived young people in a contemporary national cohort.
Ubiquitin-specific protease 11 promotes partial epithelial-to-mesenchymal transition by deubiquitinating the epidermal growth factor receptor during kidney fibrosis
Authors: Yingfeng Shi, Min Tao, Hui Chen, Xiaoyan Ma, Yi Wang, Yan Hu, Xun Zhou, Jinqing Li, Binbin Cui, Andong Qiu, Shougang Zhuang, Na Liu
Journal: Kidney International (2022)
Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications
Authors: Jagannath Mondal, Shameer Pillarisetti, Vijayabhaskarreddy Junnuthula, Monochura Saha, Seung Rim Hwang, In-kyu Park, Yong-kyu Lee
Journal: Journal of Controlled Release (2022)
Novel small molecule MRGPRX2 antagonists inhibit a murine model of allergic reaction
Authors: Mukesh Kumar, Karthi Duraisamy, Rajasekar Reddy Annapureddy, Chi Bun Chan, Billy K.C. Chow
Journal: Journal of Allergy and Clinical Immunology (2022)

Activation of Mas-related G protein-coupled receptor X2 (MRGPRX2) is a crucial non-IgE pathway for mast cell activation associated with allergic reactions and inflammation. Only a few peptides and small compounds targeting MRGPRX2 have been reported, with limited information on their pharmacologic activity.We sought to develop novel small molecule MRGPRX2 antagonists to treat MRGPRX2-mediated allergies and inflammation.A computational approach was used to design novel small molecules as MRGPRX2 antagonists. The short-listed molecules were synthesized and characterized by liquid chromatography and mass spectrometry as well as nuclear magnetic resonance. Inhibitory activity on MRGPRX2 signaling was assessed in vitro by using functional bioassays (β-hexosaminidase, calcium flux, and chemokine synthesis) and receptor activation assays (β-arrestin recruitment and Western blot analysis) in human LAD-2 mast cells and HTLA cells. In vivo effects of the novel MRGPRX2 antagonists were assessed using a mouse model of acute allergy and systemic anaphylaxis.The novel small molecules demonstrated higher binding affinity with MRGPRX2 in the docking study. The half-maximal inhibitory concentration is in the low micromolar range (5-21 μM). The small molecules inhibited not only the early phase of mast cell activation but also the late phase, associated with chemokine and prostaglandin release. Further, Western blot analysis revealed inhibition of downstream phospholipase C-γ, extracellular signal-regulated protein kinase 1/2, and Akt signaling pathway. Moreover, in the mouse models of allergies, small molecule administration effectively blocks acute, systemic allergic reactions and inflammation and prevents systemic anaphylaxis.The small molecules might hold a significant therapeutic promise to treat MRGPRX2-mediated allergies and inflammation.
Clinical, histopathologic, immunohistochemical, and electron microscopic findings in cutaneous monkeypox: A multicenter retrospective case series in Spain
Authors: Francisco José Rodríguez-Cuadrado, Laura Nájera, Dolores Suárez, Gala Silvestre, Diego García-Fresnadillo, Gaston Roustan, Laura Sánchez-Vázquez, Margarita Jo, Carlos Santonja, María Concepción Garrido-Ruiz, Ana María Vicente-Montaña, José Luis Rodríguez-Peralto, Luis Requena
Journal: Journal of the American Academy of Dermatology (2022)
Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy
Authors: Zhengyuan Yu, Hailin Tang, Shaomu Chen, Yufeng Xie, Liyan Shi, Shuhua Xia, Min Jiang, Jiaoyang Li, Dongqin Chen
Journal: Drug Resistance Updates (2022)
Corrigendum to “Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials” [Bioact. Mater. 6(3) (2021) 613–626]
Authors: Le Jiang, Zhongqun Liu, Zhaoyan Wang, Yijun Su, Yingjin Wang, Yaojie Wei, Yanan Jiang, Zhanrong Jia, Chunyang Ma, Fangli Gang, Nan Xu, Lingyun Zhao, Xiumei Wang, Qiong Wu, Xiong Lu, Xiaodan Sun
Journal: Bioactive Materials (2022)

[This corrects the article DOI: 10.1016/j.bioactmat.2020.08.035.].
A fully biodegradable polydioxanone occluder for ventricle septal defect closure
Authors: Zefu Li, Pengxu Kong, Xiang Liu, Shuyi Feng, Wenbin Ouyang, Shouzheng Wang, Xiaopeng Hu, Yongquan Xie, Fengwen Zhang, Yuxin Zhang, Rui Gao, Weiwei Wang, Xiangbin Pan
Journal: Bioactive Materials (2022)

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.
Immuno-engineered mRNA combined with cell adhesive niche for synergistic modulation of the MSC secretome
Authors: Norman Michael Drzeniek, Nourhan Kahwaji, Stephan Schlickeiser, Petra Reinke, Sven Geißler, Hans-Dieter Volk, Manfred Gossen
Journal: Biomaterials (2022)

In vitro transcribed (IVT-)mRNA has entered center stage for vaccine development due to its immune co-stimulating properties. Given the widely demonstrated safety of IVT-mRNA-based vaccines, we aimed to adopt IVT-mRNA encoding VEGF for secretory phenotype modulation of therapeutic cells. However, we observed that the immunogenicity of IVT-mRNA impairs the endogenous secretion of pro-angiogenic mediators from transfected mesenchymal stromal cells, instead inducing anti-angiogenic chemokines. This inflammatory secretome modulation limits the application potential of unmodified IVT-mRNA for cell therapy manufacturing, pro-angiogenic therapy and regenerative medicine. To uncouple immunogenicity from the protein expression functionality, we immuno-engineered IVT-mRNA with different chemically modified ribonucleotides. 5-Methoxy-uridine-modification of IVT-mRNA rescued the endogenous secretome pattern of transfected cells and prolonged secretion of IVT-mRNA-encoded VEGF. We found that high secretion of IVT-mRNA-encoded protein further depends on optimized cell adhesion. Cell encapsulation in a collagen-hyaluronic acid hydrogel increased secretion of IVT-mRNA-encoded VEGF and augmented the endogenous secretion of supporting pro-angiogenic mediators, such as HGF. Integrating minimally immunogenic mRNA technology with predesigned matrix-derived cues allows for the synergistic combination of multiple dimensions of cell manipulation and opens routes for biomaterial-based delivery of mRNA-engineered cell products. Such multimodal systems could present a more biologically relevant way to therapeutically address complex multifactorial processes such as tissue ischemia, angiogenesis, and regeneration.
Authors’ reply—A sensitivity analysis of the RAPIDO clinical trial
Authors: E.A. Dijkstra, W.H. Zwart, H. Putter, C.A.M. Marijnen, P.J. Nilsson, C.J.H. van de Velde, B. van Etten, G.A.P. Hospers, B. Glimelius
Journal: Annals of Oncology (2022)
Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives
Authors: Zi-Han Ye, Wei-Bang Yu, Mu-Yang Huang, Jun Chen, Jin-Jian Lu
Journal: Acta Pharmaceutica Sinica B (2022)

Described as a "don't eat me" signal, CD47 becomes a vital immune checkpoint in cancer. Its interaction with signal regulatory protein alpha (SIRPα) prevents macrophage phagocytosis. In recent years, a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect. Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies, indicating the combination strategy as a general trend of the future. In this review, clinical and preclinical cases about the current combination strategies targeting CD47 are collected, their underlying mechanisms of action are discussed, and ideas from future perspectives are shared.
<i>Flavonifractor plautii</i> Protects Against Elevated Arterial Stiffness
Authors: Shiyun Luo, Yawen Zhao, Shanshan Zhu, Ludi Liu, Ken Cheng, Bingqi Ye, Yueyuan Han, Jiahua Fan, Min Xia
Journal: Circulation Research (2022)

Dysbiosis of gut microbiota plays a pivotal role in vascular dysfunction and microbial diversity was reported to be inversely correlated with arterial stiffness. However, the causal role of gut microbiota in the progression of arterial stiffness and the specific species along with the molecular mechanisms underlying this change remain largely unknown.Participants with elevated arterial stiffness and normal controls free of medication were matched for age and sex. The microbial composition and metabolic capacities between the 2 groups were compared with the integration of metagenomics and metabolomics. Subsequently, Ang II (angiotensin II)-induced and humanized mouse model were employed to evaluate the protective effect of Flavonifractor plautii (F plautii) and its main effector cis-aconitic acid.Human fecal metagenomic sequencing revealed a significantly high abundance and centrality of F plautii in normal controls, which was absent in the microbial community of subjects with elevated arterial stiffness. Moreover, blood pressure only mediated part of the effect of F plautii on lower arterial stiffness. The microbiome of normal controls exhibited an enhanced capacity for glycolysis and polysaccharide degradation, whereas, those of subjects with increased arterial stiffness were characterized by increased biosynthesis of fatty acids and aromatic amino acids. Integrative analysis with metabolomics profiling further suggested that increased cis-aconitic acid served as the main effector for the protective effect of F plautii against arterial stiffness. Replenishment with F plautii and cis-aconitic acid improved elastic fiber network and reversed increased pulse wave velocity through the suppression of MMP-2 (matrix metalloproteinase-2) and inhibition of MCP-1 (monocyte chemoattractant protein-1) and NF-κB (nuclear factor kappa-B) activation in both Ang II-induced and humanized model of arterial stiffness.Our translational study identifies a novel link between F plautii and arterial function and raises the possibility of sustaining vascular health by targeting gut microbiota.
Hydrogen Sulfide Modulates Endothelial–Mesenchymal Transition in Heart Failure
Authors: Zhen Li, Huijing Xia, Thomas E. Sharp, Kyle B. LaPenna, Antonia Katsouda, John W. Elrod, Josef Pfeilschifter, Karl-Friedrich Beck, Shi Xu, Ming Xian, Traci T. Goodchild, Andreas Papapetropoulos, David J. Lefer
Journal: Circulation Research (2022)

Hydrogen sulfide is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure. Cystathionine γ-lyase (CSE), 1 of 3 hydrogen-sulfide-producing enzyme, is predominantly localized in the vascular endothelium. The interaction between the endothelial CSE-hydrogen sulfide axis and endothelial-mesenchymal transition, an important pathological process contributing to the formation of fibrosis, has yet to be investigated. Endothelial-cell-specific CSE knockout and Endothelial cell-CSE overexpressing mice were subjected to transverse aortic constriction to induce heart failure with reduced ejection fraction. Cardiac function, vascular reactivity, and treadmill exercise capacity were measured to determine the severity of heart failure. Histological and gene expression analyses were performed to investigate changes in cardiac fibrosis and the activation of endothelial-mesenchymal transition. Endothelial-cell-specific CSE knockout mice exhibited increased endothelial-mesenchymal transition and reduced nitric oxide bioavailability in the myocardium, which was associated with increased cardiac fibrosis, impaired cardiac and vascular function, and worsened exercise performance. In contrast, genetic overexpression of CSE in endothelial cells led to increased myocardial nitric oxide, decreased endothelial-mesenchymal transition and cardiac fibrosis, preserved cardiac and endothelial function, and improved exercise capacity. Our data demonstrate that endothelial CSE modulates endothelial-mesenchymal transition and ameliorate the severity of pressure-overload-induced heart failure, in part, through nitric oxide-related mechanisms. These data further suggest that endothelium-derived hydrogen sulfide is a potential therapeutic for the treatment of heart failure with reduced ejection fraction.
Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil As the New Standard for Graft-Versus-Host Disease (GVHD) Prophylaxis in Reduced Intensity Conditioning: Results from Phase III BMT CTN 1703
Authors: Shernan G Holtan, Mehdi Hamadani, Juan WU, Monzr M. AL Malki, Lyndsey Runaas, Hany Elmariah, Andrew R. Rezvani, Mahasweta Gooptu, Karilyn T. Larkin, Brian C. Shaffer, Najla H El Jurdi, Alison W. Loren, Melhem Solh, Aric C. Hall, Amin M Alousi, Omer H Jamy, Miguel-Angel Perales, Janny M. Yao, Kristy Applegate, Ami S. Bhatt, Leslie S. Kean, Yvonne A. Efebera, Carrie Lynn Kitko, Ran Reshef, William Clark, Nancy L. DiFronzo, Lori Henderson, Richard J. Jones, Eric Liefer, Michael J Martens, Mary M. Horowitz, Javier Bolanos-Meade
Journal: Blood (2022)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Cervical cancer is among the most common malignancies worldwide.A significant proportion of patients present with locally advanced disease (FIGO stage IB-IVA) that is treated with chemoradiotherapy with curative intent.Tumor hypoxia is associated with poor response to radiotherapy; despite advances in radiotherapy techniques, many women with cervical cancer develop recurrence.The authors previously demonstrated that metformin can decrease tumor hypoxia and consequently increase radiation response in vivo.Here, Han and colleagues present data from a phase II, window-of-opportunity trial that investigated if metformin decreased tumor hypoxia in patients with locally advanced cervical cancer.In this trial that selected for patients with hypoxic tumor, metformin decreased cervical tumor hypoxia without significant toxicity.The additional FAZA-PET scans and tumor biopsies limited study accrual, and more pragmatic ways of measuring and selecting tumor hypoxia are needed for future studies.
Abortion and Mental Health—Context and Common Ground
Authors: Tyler J. VanderWeele
Journal: JAMA Psychiatry (2022)

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Biodiversity: the overlooked source of human health
Authors: Yuliya Linhares, Alexander Kaganski, Christian Agyare, Isil A. Kurnaz, Vidushi Neergheen, Bartlomiej Kolodziejczyk, Monika Kędra, Muhammad Wahajuddin, Lahcen El-Youssf, Thomas Edison dela Cruz, Yusuf Baran, Milica Pešić, Uttam Shrestha, Rigers Bakiu, Pierre-Marie Allard, Stanislav Rybtsov, Myrtani Pieri, Velia Siciliano, Yensi Flores Bueso
Journal: Trends in Molecular Medicine (2022)
AI in the hands of imperfect users
Authors: Kristin M. Kostick-Quenet, Sara Gerke
Journal: npj Digital Medicine (2022)

As the use of artificial intelligence and machine learning (AI/ML) continues to expand in healthcare, much attention has been given to mitigating bias in algorithms to ensure they are employed fairly and transparently. Less attention has fallen to addressing potential bias among AI/ML's human users or factors that influence user reliance. We argue for a systematic approach to identifying the existence and impacts of user biases while using AI/ML tools and call for the development of embedded interface design features, drawing on insights from decision science and behavioral economics, to nudge users towards more critical and reflective decision making using AI/ML.
The ability of noninvasive methods to detect and quantify laryngeal obstruction
Authors: U Hoijer, H Ejnell, B Bake
Journal: European Respiratory Journal (1991)

The ability of the noninvasive methods forced oscillation technique (Rosc), spirometry and flow-volume curves to detect and quantify laryngeal obstruction, using assessment of orolaryngeal (upper) airway resistance (Rol) as reference, was compared in 55 patients with various laryngeal diseases. Statistical analysis was performed by means of sensitivity/specificity, simple regression, stepwise regression and stepwise logistic regression. The results showed that the ability to detect a laryngeal obstruction was acceptable and that Rosc-Insp, peak inspiratory flow (PIF) and forced inspiratory volume in one second (FIV1) seemed to be the best variables for detection of a laryngeal obstruction. None of the studied noninvasive methods appeared to be adequate for quantification of laryngeal obstruction.